A very simple model system, the cellular slime mold, Dictyostelium discoideum, is being used to study the mechanisms which control developmental gene activation during normal differentiation. Because of the similarity of basic regulatory mechanisms, this system represents an attractive alternative to animal research. During growth and the early stages of aggregation Dictyostelium cells express 50-55% of their single copy genome as mRNA and HnRNA. An additional 26% of the single copy genome is expressed only during the late stages of development. Initiation of transcription on the late portion of the genome requires cell-cell interaction and cAMP. Because such a high proportion of this small eukaryotic genome is either constitutively transcribed or developmentally induced, it offers a unique opportunity to study the structural organization in chromatin of transcriptionally active genes. Our results indicate that both the constitutively expressed and developmentally inducible genes are in a DNase I-sensitive, active structure in chromatin regardless of whether the developmentally inducible genes are being transcribed. By contrast, micrococcal nuclease has been used to identify a structural organization unique to genes which are actually in the process of being transcribed. Properties of this organization have been used to resolve oligonucleosomes specifically derived from actively transcribed genes and to determine their protein composition. Nucleosomes from transcriptionally active genes are devoid of histone H1, while those from inactive genes contain H1.